Objectives:Hydrogen sulfide(H2S)has been proposed as a gasotransmitter similar to nitric oxide(NO)and carbon monoxide(CO).It has been proved to play important biologic roles in the regulation of gastrointestinal *** p...
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Objectives:Hydrogen sulfide(H2S)has been proposed as a gasotransmitter similar to nitric oxide(NO)and carbon monoxide(CO).It has been proved to play important biologic roles in the regulation of gastrointestinal *** present study was to explore the effect of hydrogen sulfide on smooth muscle motility in the gastric ***:The immunocytochemistry technique was used to characterize the expression of cystathionineβ-synthase(CBS)and cystathionineγ-lyase(CSE)in cultured smooth muscle cells from the gastric *** smooth muscle motility was recorded by isometric force *** recordings,whole-cell patch clamp technique and calcium imaging were used to investigate the mechanism by which hydrogen sulfide regulates gastric fundus ***:We found that both CBS and CSE were expressed in the cultured smooth muscle cells from the gastric fundus and that H2S increased the smooth muscle tension of the gastric fundus in mice at a low concentration(<300μM).In addition,AOAA,a CBS inhibitor,reduced the tension,whereas L-NAME,a nonspecific nitric oxide synthase(NOS),increased the *** AOAA-induced relaxation was significantly recovered by H2S,and the Na HS-induced increase in tonic contraction was blocked by 5 m M 4-aminopyridine(4-AP)and 1μM *** HS significantly depolarized the membrane potential and inhibited the voltage-dependent potassium ***,Na HS increased L-type Ca2+currents and caused an elevation in intracellular calcium([Ca2+]i).Conclusions:The results suggest that H2S may be an excitatory modulator in gastric fundus in mice and the excitatory effect of H2S on gastric fundus smooth muscle is mediated by voltage-dependent potassium and L-type calcium channels.
The hyperpolarisation activated c AMP-gated cation channels(HCNs)belong to the cyclic nucleotide-gated(CNG)channel family and consist of four subtypes,*** channels are known to be expressed in the heart where they pla...
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The hyperpolarisation activated c AMP-gated cation channels(HCNs)belong to the cyclic nucleotide-gated(CNG)channel family and consist of four subtypes,*** channels are known to be expressed in the heart where they play important roles in the generation of the cardiac *** of HCNs are also expressed in non-cardiac *** have previously shown that HCN2 and HCN3 were differentially expressed in spinal and vagal primary afferent neurons of the small *** blockers attenuated the vagal component of the mesenteric afferent response to distension of the normal ***,HCNs appeared to play a role in priming the vagal but not spinal afferents in the normal *** this work we further investigated the possible expression and function of HCNs within the *** staining showed HCNs being distinctively expressed in the enterochromaffin(EC)cells of the mice,the rat and the human *** then investigated the possible role of HCNs in regulation of 5-HT release through real-time amperometric measurement in an isolated murine gut *** AMP was shown to increase 5-HT release and the mesenteric afferent nerve *** effect was reversible by HCN blockers,ZD7288 and Cs Cl,which could also inhibit the basal 5-HT release.5-HT3 receptor antagonist,tropisetron,also blocked the afferent nerve response to c *** cholera toxin(CT)is known to increase c AMP level and 5-HT release,we tested whether activation of HCNs might underlie CT-induced 5-HT release and afferent nerve *** expected,CT caused a slowly developing increase in 5-HT release and afferent nerve activity,which were reversed by ***,tropisetron was able to inhibit CT-induced afferent *** results suggest that HCNs drive serotonin release and afferent nerve activity in the *** propose HCNs might represent a novel therapeutic target for inflammatory or functional bowl diseases.
Objectives:H2S has been shown to have an excitatory effect on gastric motility,but the underlying molecular mechanism is *** this study,we aimed to investigate the possible targets of H2S and how H2S affects its targe...
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Objectives:H2S has been shown to have an excitatory effect on gastric motility,but the underlying molecular mechanism is *** this study,we aimed to investigate the possible targets of H2S and how H2S affects its target proteins during H2S-induced contraction using electrophysiological and molecular biological ***:The potassium channel currents were recorded from freshly isolated gastric smooth muscle and H293 cells by using whole-cell patch clamp technique and membrane potential was measured by using voltage fluorescent ***:The results demonstrated that exogenous H2S enhanced the basal tension of gastric antral smooth muscle,and 4-AP,a selective voltage-dependent potassium channel(KV)blocker,abolished the excitatory effect of Na ***(DTT),a reducing agent,also inhibited the Na HS-induced enhancement of basal tension.A patch-clamp experiment showed that Na HS inhibited the fast inactivation component of the voltage-dependent potassium channel current(IKVfast)in isolated gastric antral smooth muscle cells but did not affect the slow inactivation component(IKVslow).Na HS inhibited the KV4.3 current,which contributes greatly to IKVfast in H293 cells with heterologous expression,but did not inhibit the KV4.1 and KV4.2 currents,which together contribute greatly to *** HS significantly depolarized the membrane potential in cultured gastric smooth muscle cells,but the Na HS-induced depolarization was suppressed by knockdown of KV4.3 and N-ethylamaleimide(NEM),a free thiol group *** addition,Na HS sulfhydrated KV4.3 in H293 cells with heterologous expression as well as in gastric smooth muscle ***,this S-sulfhydration was inhibited by NEM and *** Na HS-induced inhibition of IKVfast and KV4.3 was also blocked by NEM and ***:These results suggest that exogenous H2S sulfhydrates KV4.3 to depolarize the membrane potential,thereby enhancing the basal tension of gastric antral smooth muscle.
Objectives:Angiotensin Ⅱ(AngⅡ)as local hormone in gastrointestinal tract play an important role in regulation of smooth muscle motility and smooth muscle ***,it is not clear whether Ang Ⅱ is involved in diabetics-i...
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Objectives:Angiotensin Ⅱ(AngⅡ)as local hormone in gastrointestinal tract play an important role in regulation of smooth muscle motility and smooth muscle ***,it is not clear whether Ang Ⅱ is involved in diabetics-induced loss of gastric *** present study was designed to investigate the relationship between diabetics-induced loss of gastric ICC and Ang Ⅱ signaling pathway in streptozotocin(STZ)-induced diabetic ***:The angiotensin converting enzyme(ACE)expression in gastric mucosa and Ang Ⅱ type 1 receptor(AT1R)expression in gastric smooth muscle tissue were observed by using western blot method in normal and diabetic *** effect of Ang Ⅱ on the m SCF expression of gastric smooth muscle cells was investigated by using western blot ***:The results indicated that the protein expressions of c-Kit and membrane-bound stem cell factor(m SCF)in gastric smooth muscle were decreased in STZ-induced diabetic ***,expressions of AT1R in gastric smooth muscle and ACE in gastric mucosa were *** effect of Ang Ⅱ on the gastric smooth muscle tonic contraction was potentiated in diabetic *** Ⅱ increased the m SCF expression in the cultured gastric smooth muscle cells(GSMCs)and also promoted cell proliferation in cultured GSMCs in a dose-depend ***,a pharmacological inhibitors of phosphoinositide-3 kinase(PI3k),and ZD7155,an AT1R blocker,inhibited Ang Ⅱ-induced increase of m SCF in cultured ***:These results suggest that up-regulation of RAS maybe a protective factor against ICC loss which mediated by PI3K/Akt signaling pathway in STZ-induced diabetic mice.
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